One objective of these investigations was to study the factors responsible for maintaining the structural integrity of hemoglobins in solution and in the erythrocyte. This information will provide the frame of reference necessary to resolve the factors involved in the nucleation step in the sickling phenomenon which are as follows: (1) physiological agents which can cause structural alterations of the protein which in turn can trigger a substantial denaturation of the protein under stress conditions and (2) the change in the biological milieu involved in promoting the initial aggregation and/or precipitation process. One of the techniques employed in our laboratory is microdilatometry. Volume effects can be determined both on a kinetic scale and under equilibrium conditions. This methodology and the analysis of the data is an area which this laboratory has pioneered. This investigation deals with the effect of relatively small changes of the ionic composition, both anionic and cationic, on the stability of hemoproteins. Comparative studies were performed on the single-chain myoglobin and the four double bond subunit hemoglobin to establish the influence of specific agents on the quaternary structure of these proteins via the change of the partial molar volume of these entities. These results are important not only with respect to understanding the physiological process but also because there is no relevant literature existing in this area. Bibliographic references: Volume Effects Produced by Protein-Ion Interactions. The Binding of Bovine Plasma Albumin with Thiocyanate and Trichloroacetate Ions. Sam Katz, Jack K. Crissman, and Linda Carol Roberson, J. Biol. Chem. (1974). 249, 7892-7895. Threonine Inhibition of the Aspartokinase-Homoserine Dehydrogenase-I Complex of Escherichia coli: Dilatometric Studies. Eugene Wampler and Sam Katz. Biochim. Biophys. Acta. (1974). 365, 414-417.